Predicting and Diagnosing Patients With Autoimmune Disease

a technology for predicting and diagnosing patients with autoimmune diseases, applied in the field of molecular biology, pathology and genetics, can solve the problems of complete debilitation and death, mild discomfort for patients, and continue to provide a considerable challenge to the healthcare industry, and achieve the effect of increasing risk

Inactive Publication Date: 2009-10-01
SAWALHA AMR H +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]Thus, in accordance with the present invention, there is provided a method of identifying a subject afflicted with or at risk of developing systemic lupus erythematosus comprising (a) obtaining a nucleic acid-containing sample from said subject; (b) determining the presence or absence of a single nucleotide polymorphism (SNP) in MECP2, wherein the presence of a SNP in MECP2 associated with increased risk of an autoimmune disease indicates that said subject is afflicted or at risk of developing SLE. The method may further comprise analyzing a second, third or fourth SNP from MECP2. The SNP may selected from the group consisting of rs17435, rs1734787, rs1734792, and rs1734791, and four of these SNPs may be assessed. The SNP may be in linkage disequilibrium with rs17435, rs1734787, rs1734792, and / or rs1734791. The method may further comprise treating said subject based on the results of step (b). The method may also further comprise taking a clinical history from said subject.

Problems solved by technology

These diseases can cause symptoms ranging from only mild discomfort to the patient, to complete debilitation and death.
As such, they continue to provide a considerable challenge to the healthcare industry.
Moreover, they are usually affected by environmental factors as well.
The situation is not aided by clinical diagnosis, since (a) familial autoimmune disease is often characterized by related individuals suffering from distinct autoimmune defects, and (b) the same autoimmune disease may manifest itself differently in different individuals at different times. Thus, one is left with a difficult, if not impossible, clinical diagnosis even when some genetic information is available.
Although the crucial role of genetic predisposition in susceptibility to SLE has been known for decades, only minimal progress has been made towards elucidating the specific genes involved in human disease.

Method used

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  • Predicting and Diagnosing Patients With Autoimmune Disease
  • Predicting and Diagnosing Patients With Autoimmune Disease
  • Predicting and Diagnosing Patients With Autoimmune Disease

Examples

Experimental program
Comparison scheme
Effect test

example 1

Methods

[0157]SLE patients and controls. Korean SLE patients and controls were recruited at the Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea. All patients were of Korean descent and met the 1997 American College of Rheumatology SLE classification criteria. A total of 628 independent female SLE patients and 736 healthy unrelated female controls were studied. No two SLE patients or two controls are blood relatives to avoid intrafamilial correlation bias. Another independent cohort of SLE patients of European descent was studied. This cohort consisted of 1080 independent cases and 1080 healthy unrelated controls matched for race and sex and recruited in the SLE genetics studies at the Oklahoma Medical Research Foundation as well as from collaborators in the United States, United Kingdom, and Sweden. This cohort included 928 females and 152 males in each of the case and control groups. All SLE patients met the 1997 American College of Rheumatology SLE classification ...

example 2

Results

[0161]The inventors initially genotyped 628 Korean female SLE patients and 736 healthy female Korean controls across 21 single nucleotide polymorphisms (SNPs) located within or around MECP2 (Table 1). Nine SNPs had a minor allele frequency of more than 5% in our Korean cohort and were used for further analysis. All 9 SNPs were within expected Hardy-Weinberg proportions in both cases and controls (Table 2). Eight out of the nine SNPs are within the MECP2 gene and showed significant association with SLE (Table 2 and FIG. 1). The SNP having the strongest association in the Korean SLE patients is rs17435 (Chi2=22.83, OR=1.58, p=0.0000018) followed by rs1734787 (Chi2=21.58, OR=1.55, p=0.0000034), rs1734792 (Chi2=20.68, OR=1.53, p=0.0000054) and rs1734791 (Chi2=18.70, OR=1.51, p=0.000015). The SNPs rs1734787, rs1734792, and rs1734791 are all in linkage disequilibrium with rs17435 (r2=0.88, 0.92, and 0.86, respectively).

[0162]The inventors next performed haplotype-based association ...

example 3

Discussion

[0165]DNA methylation plays a critical role in tissue differentiation, imprinting, transcriptional suppression of parasitic DNA, silencing of transcriptional “noise,” and X-chromosome inactivation (Bird, 1993). Utilizing a candidate gene approach, the inventors first identified significant association with MECP2 SNPs and SLE in a cohort of Korean SLE patients and controls. Next, they replicated the association with MECP2 SNPs in an independent cohort of SLE patients and controls of European descent. Indeed, the disease-associated alleles in rs17435, rs1734787, rs1734792, and rs1734791 (T, C, A, and A respectively) have meta analysis p values of 1.2×10−8, 1.6×10−8, 3.3×10−8, and 7.2×10−8 respectively (Table 7). Interestingly, the disease associated alleles in these four MECP2 SNPs are 4 times more common in Korean as compared to European-derived controls. This might suggest a possible explanation for the higher frequency of SLE in people of Asian descent as compared to Euro...

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Abstract

The present invention provides methods for the prediction and diagnosis of autoimmune diseases, including Systemic Lupus Erythematosus, by identifying polymorphisms in the gene for MECP2.

Description

PRIORITY CLAIM[0001]This application claims benefit of priority to U.S. Provisional Application Ser. No. 61 / 028,972, filed Feb. 15, 2008, the entire contents of which are hereby incorporated by reference.FEDERAL GRANT SUPPORT[0002]This invention was made with grant support under grant nos. AR42460, AI024717, AI31584, AR62277, AR048940, AR0490084, P20-RR015577 and P20-RR023477 from the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]A. Field of the Invention[0004]The present invention relates to the fields of molecular biology, pathology and genetics. More specifically, the invention relates to methods of predicting and diagnosing automimmune disease based on polymorphisms in the MECP2 gene.[0005]B. Related Art[0006]Autoimmune diseases comprises a large number of widely varying illnesses. Their common feature is the existence of an immune response in the subject against one or more “self” antigens, including such wide...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68G01N33/566
CPCC12Q1/6876G01N33/564C12Q2600/156
Inventor SAWALHA, AMR H.HARLEY, JOHN B.
Owner SAWALHA AMR H
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